Depressive symptoms during pregnancy and low birth weight at term: Longitudinal study

There is conflicting evidence regarding the effect of depressionduring pregnancy on birth weight. We used data from the AvonLongitudinal Study of Parents and Children to investigate whetherdepressive symptoms during pregnancy in 10 967 women led tolow birth weight at term in their offspring. Those with a highdepressive symptom score during pregnancy were more likely tohave babies of low birth weight (95% CI 1.16-2.40, P<0.01),but this attenuated after adjustment for confounders (OR=1.29,95%CI 0.87-1.91, P=0.210). Hence there is little evidence of anindependent association between depressive symptoms duringpregnancy and birth weight.

INTRODUCTION

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INTRODUCTION

Low birth weight at term is a marker of intrauterine growthrestriction and can result from prenatal exposure to high maternallevels of steroids (Gur et al, 2004). As maternal stress resultsin raised cortisol, psychological symptoms during pregnancymay cause intrauterine growth restriction. Depression and anxiety are common during pregnancy, but evidence for any effect onintrauterine growth is conflicting (e.g. Kelly et al, 2002;Andersson et al, 2004). In this large prospective study weinvestigated whether mothers with symptoms of depression andanxiety during the second trimester of pregnancy are at greaterrisk of having babies of low birth weight at term.

METHOD

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METHOD

We used data collected as part of the Avon Longitudinal Studyof Parents and Children (ALSPAC; http://www.alspac.bris.ac.uk). In total, 14 541 women were enrolled and 13 194 (90.7%) completeda questionnaire at 18 weeks' gestation.

Questionnaires included the Edinburgh Postnatal Depression Scale(EPDS; Cox et al, 1987) and sub-scales of the Crown-CrispExperiential Index (CCEI), which measures `free-floating' anxiety(Crisp et al, 1978) which were completed at 18 and 32 weeksof pregnancy. The EPDS has been validated for use during pregnancyand at other times (Murray & Cox, 1990; Shakespeare, 2001).The CCEI correlates well with other measures of anxiety inwomen during pregnancy and the internal consistency exceeds0.8.

Birth weight was obtained directly by research staff. We includedonly those babies delivered between 37 and 43 weeks' inclusiveand we excluded multiple births as these babies are more likelyto be of lower birth weight.

Data on confounding factors came from the self-report postalquestionnaires and included gender of the baby, gestationalage, smoking, maternal age, parity, educational level, alcoholand caffeine use during pregnancy, chronic disease, pre-pregnancybody mass index, ethnicity and a history of miscarriage, Caesareansection, prior low birth weight, or preterm births.

We used linear and logistic regression analyses with birth weightas a continuous outcome or dichotomised as low birth weight(<2500 g) at term. We used the multiple imputation by chainedequation method to impute missing data for confounders (van Buuren et al, 1999).

RESULTS

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RESULTS

Analyses were performed on 10 967 women, of whom 1519 (13.9%,95% CI 13.2-14.5%) scored >12 on the EPDS at 18 weeks ofpregnancy, indicating a likely diagnosis of depression. Therewere 8427 (76.8%) women with complete data on all confoundingvariables. We imputed missing data on confounders in all adjustedanalyses.

Women scoring >12 on the EPDS at 18 weeks of pregnancy hadbabies that were 33.8 g lighter (95% CI 8.0-59.7, P=0.01) comparedwith women with an EPDS score <13. Following adjustmentfor confounders, an EPDS score >12 was no longer significantlyassociated with birth weight: babies born to mothers with probabledepression were 1.1 g lighter (95% CI -22.1 to 24.3, P=0.4).The strongest confounder appeared to be smoking. The coefficientfollowing adjustment for gender, maternal age and gestationwas -25.9 (95% CI -49.9 to -2.02), this dropped to -1.0 (95%CI -24.9 to 22.9) following additional adjustment for smoking.Using anxiety as the exposure variable we found similar results(details available from the authors).

Following adjustment, there was no effect restricted to thosewith higher symptom scores; mothers scoring $>=$ 16 on the EPDSat 18 weeks of pregnancy had babies that were 22.5 g lighter(95% CI -12.5 to 57.4, P=0.207) than those scoring <13.

We repeated these analyses with the outcome categorised intolow birth weight at term according to the traditional definitionof <2500 g) (Fig. 1). The drop in the estimated odds ratiowas greatest following adjustment for smoking. The odds ratiofollowing adjustment for gender, gestation and maternal agewas 1.57 (95% CI 1.08-2.29), dropping to 1.38 (95% CI 0.94-2.01)after adjustment for smoking.

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Fig. 1 Odds ratio of low birth weight for offspring of mothers with depression at 18 weeks of pregnancy: effect of adding confounders comparing complete data and including missing data imputed using multiple imputation by chained equation (MICE); — ${diamondsuit}$ —, percentage with missing data when confounders added consecutively; — ${blacktriangleup}$ —, complete data; — ${blacksquare}$ —, MICE estimate. LBW, low birth weight; BMI, body mass index.

With anxiety as the exposure variable we found very similarresults to those seen for depression (details available fromthe authors). We found a weak association with prolonged exposureto depressive symptoms. Those scoring >12 on the EPDS atboth 18 and 32 weeks of pregnancy had babies that were 40.2g lighter (95% CI 3.8-76.6, P<0.05) than those with an EPDS score <13 at both times. This association diminished andwas no longer statistically significant following adjustment.

DISCUSSION

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DISCUSSION

This is the largest longitudinal study investigating the association between maternal mood during pregnancy and low birth weight.We found no evidence to support an independent associationbetween depressive or anxiety symptoms during pregnancy andlow birth weight at term. There is a widespread assumptionthat depression and anxiety during pregnancy can impair intrauterinegrowth. This study challenges that assumption.

This study was large enough to ensure that we could detect smalleffects. The findings are limited by the use of a self-reportmeasure for depression and by the loss of data from a quarterof participants because of missing data on confounding variables.We conducted sensitivity analyses using multiple imputationfor missing data. There was little difference between the results from the analyses using only available data and those includingimputed data, suggesting that missing data were unlikely tohave substantially biased our findings.

One large retrospective study that found an association betweenpsychiatric disorder at discharge and low birth weight didnot measure important confounders such as smoking and was restrictedto those with severe mental illness (Kelly et al, 2002). Somesmaller prospective studies (Copper et al, 1996; Chung et al, 2001; Andersson et al, 2004) reported no association of depressionin pregnancy and various measures of intrauterine growth restriction,although one (Copper et al, 1996) reported an associationof low birth weight with a measure of perceived stress duringpregnancy. These studies were too small to exclude modest effectsand interpretation is complicated by the inclusion of pretermbirths. Some studies have found an association between depressivesymptoms and preterm birth (Orr et al, 2002). Adjusting forgestation might not be sufficient to distinguish risk factors for intrauterine growth restriction from those for pretermbirth. We addressed this problem by restricting our analysesto babies born at term.

In this study we adjusted for a range of confounding variablesincluding smoking. It remains possible that smoking lies onthe causal pathway between depression and intrauterine growthrestriction. Adjustment for smoking removed any evidence ofa direct association between mean birth weight at term and moodduring pregnancy.

Although a woman with a high depressive symptom score in themid trimester of pregnancy has a slightly increased risk ofhaving a low birth weight infant, this is most likely to beowing to health behaviours associated with depressive symptoms.

Low birth weight at term is only one marker of foetal development.Studies in animals suggest there are long-term effects of exposureto prenatal stress (Barbazanges et al, 1996). It is possiblethat psychological symptoms during pregnancy have other effectson development of offspring that only become apparent after birth. This remains an important area for investigation (O'Connor et al, 2002).

REFERENCES

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